Related Experiment Video

Updated: Aug 25, 2026

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

p27 binds cyclin-CDK complexes through a sequential mechanism involving binding-induced protein folding

Eilyn R Lacy1, Igor Filippov, William S Lewis

  • 1Department of Structural Biology, St. Jude Children's Research Hospital, 332, North Lauderdale Street, Memphis, Tennessee 38105, USA.

Nature Structural & Molecular Biology
|March 17, 2004
PubMed

Insights

The protein p27 regulates cell proliferation by binding to cyclin-dependent kinases (CDKs). This study reveals p27 has nascent secondary structures and folds upon binding, a mechanism key to its cell cycle control functions.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • The protein p27 (also known as CDKN1B) is a key regulator of cell proliferation.
  • It functions by inhibiting nuclear cyclin-dependent kinases (CDKs), which are critical for cell cycle progression.
  • p27 also interacts with various other cellular targets, indicating diverse biological roles.

Purpose of the Study:

  • To elucidate the structural and dynamic properties of p27 that underpin its multifaceted functions.
  • To understand the molecular mechanisms by which p27 interacts with its targets, particularly CDK-cyclin complexes.

Main Methods:

  • Investigated the structural characteristics of p27, including its intrinsic disorder and nascent secondary structure.
  • Utilized kinetic analyses to determine the mechanism of p27 binding to Cdk2-cyclin A.
  • Examined the specificity of p27 interactions with different CDK-cyclin complexes.

Main Results:

  • p27 exhibits intrinsic disorder but possesses nascent secondary structure that may aid in molecular recognition.
  • Binding to Cdk2-cyclin A induces p27 folding, with kinetics suggesting an initial interaction with cyclin A.
  • p27 specifically targets CDK-cyclin complexes involved in cell cycle control, not closely related CDKs.

Conclusions:

  • p27's interaction with cyclin A is crucial for its specificity and function in regulating cell cycle progression.
  • The findings suggest a sequential, folding-on-binding mechanism for p27's activity.
  • Homologous proteins p21 and p57 likely employ similar mechanisms for their cell cycle regulatory functions.

More Related Videos

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis08:33

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis

Published on: December 5, 2017

Related Concept Videos

Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
Positive Regulator Molecules01:45

Positive Regulator Molecules

To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...